Zfp281 safeguards directionality of developmental progression analogously to a rectifier diode, which passes electric current in one direction only.
Animal development is a unidirectional process that steers undifferentiated cells of the early embryo into specialized cell types such as brain, muscle or skin cells. Once differentiated, there is almost no way back. A notable exception is the de-differentiation of mature into immature cell types during injured tissue regeneration. It is unknown if the reversal of cellular specialization proceeds along the same path used by natural development - in reverse direction - or along distinct paths. The Betschinger group has now uncovered a bi-directional and reversible differentiation mechanism, shedding light on how developmental unidirectionality is safeguarded. Although humans have some tissue regeneration capacities, for example to repair skin or cartilage after injury, those are very limited compared to other animals, such as salamanders, that can rebuild entire limbs upon amputation. It has long been thought that humans, like most mammals, are poor regenerators because the development and maturation of adult cell types is irreversible, thus preventing de-differentiation into cell types that are able to reform tissues. However, this view radically changed when Shinya Yamanaka (awarded with the Nobel Prize in Physiology or Medicine 2012 for that discovery) demonstrated that adult mammalian cells can be experimentally reprogrammed into pluripotent stem cells, capable of differentiating into any adult cell type. Therefore, poor regeneration is not due to an inability of our cells to de-differentiate, but because this process is actively restricted. Molecular mechanisms that limit de-differentiation have already been identified, but a fundamental question remains: To what extent is de-differentiation a reversion of natural development?
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